Exosomes, linked to tumor metastasis, are secreted in the hypoxic microenvironment and enriched with miRNA-301a-3p, phosphatases, and the angiotensin II/PI3Kγ signaling pathway, which induce HIF1-α or HIF2-α to stimulate M2 macrophage polarization, thereby promoting tumor cell metastasis (34, 110). Here, EPAS1 is linked to neoplasm.